Introduction: Tumours are more likely to metastasize after the development of resistance to EGFR-TKIs. CD146 is a multifunctional molecule and is implicated in tumour invasion and metastasis; however, its role in lung cancer has not been clearly established.
Objective: Here, we aimed to explore the relationship between CD146 pathway and stem cell phenotype after EGFR-TKI resistance in lung cancer.
Methods: EGFR-TKI-resistant cell lines were established by exposing parental cells to erlotinib/gefitinib. The CD146 level was measured by a western blot, RT-PCR and immunocytochemistry fluorescent. Cell migration was examined by the transwell assay and the scratch assay. Stemness phenotype genes were evaluated by RT-PCR and stem cell phenotype was observed by the microsphere formation assay.
Results: CD146 and stemness phenotype genes increased while β-catenin decreased in acquired EGFR-TKI-resistant cell lines. CD146's over-expression induced the up-regulation of stemness-related genes and was inversely correlated with the β-catenin expression, which further increased the migration capability of resistant cancer cells. CD146's knockdown suppressed cell migration and stemness phenotype.
Conclusions: CD146 molecule contributes to the stemness phenotype and migration in EGFR-TKI-resistant cells. CD146 might be a potential therapeutic target for EGFR-TKI-resistant lung cancer or metastasis prevention.
Keywords: CD146; EGFR-TKI resistance; invasion and metastasis; lung cancer; stemness phenotype.
© 2018 John Wiley & Sons Ltd.